Cannabinoid CB₁ receptor‐mediated modulation of evoked dopamine release and of adenylyl cyclase activity in the human neocortex

Abstract

1 The present study investigated the binding characteristics of various ligands to cannabinoid CB 1 receptors in human neocortex and amygdala. In addition, the functionality of CB 1 receptors in the human neocortex was assessed by examining the effects of CB 1 receptor ligands on evoked

Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use

“…Animal experiments documenting a link between dopamine D 2 receptor activation and anandamide release support this hypothesis. Direct agonists of D 2 -like dopamine receptors, such as quinpirole or apomorphine, or indirect dopamine agonists, such as cocaine, stimulate anandamide formation in the dorsal striatum and other basal ganglia structures of the rat brain (Centonze et al, 2004;Ferrer et al, 2003;Giuffrida et al, 1999;Steffens et al, 2004). As acute psychoses may be associated in humans with region-specific alterations in dopamine neurotransmission (Frankle et al, 2003;Laruelle et al, 1999Laruelle et al, , 2003, it is reasonable to hypothesize that the increased CSF anandamide concentrations observed in firstepisode schizophrenics may be a consequence, albeit not necessarily a direct one, of aberrant dopaminergic activity.…”

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

“…It has been shown in neurochemical experiments that exogenous cannabinoids inhibit the release of radiolabeled acetylcholine (Steffens et al, 2003b), GABA (Katona et al, 2000), noradrenaline (Schlicker et al, 1997), and dopamine (Steffens et al, 2004) from axon terminals in human brain slices. To our knowledge, there is only one study in which the effect of an exogenous cannabinoid on 'synaptic transmission' (instead of chemically measured transmitter release) in the human brain has been examined: Nakatsuka et al (2003) have shown that an exogenous cannabinoid agonist inhibits GABAergic synaptic transmission in the hippocampus.…”

Functional Pharmacology in Human Brain

“…According to Steffens et al (2003), the facilitatory effect of SR141716 on the release of ACh in the human neocortex suggests that cannabinoid CB 1 receptor antagonists may be useful in the treatment of dementia. Steffens et al (2004) (Hermann et al, 2002), indicating that the rodent brain may not represent a suitable model to investigate cannabinoid-dopamine interactions in the neocortex.…”

“…Again AM251 was ineffective on DA release in the rat. One likely explanation for the AM251 effect is the disruption of an endocannabinoid tone that keeps the release of DA in human neocortex partly depressed (Steffens et al, 2004).…”

“…Steffens et al (2004) speculated that CB 1 receptor activation may depress DA release not only by impairing the function of VSCCs but also by inhibiting adenylyl cyclase. Whether VSCCs and adenylyl cyclase are functionally connected in nerve terminals remains to be established.…”